{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T12:53:50Z","timestamp":1771505630046,"version":"3.50.1"},"reference-count":38,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2002,12,3]],"date-time":"2002-12-03T00:00:00Z","timestamp":1038873600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2002,12,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>Although experimental studies have demonstrated an important role of insulin\u2010like growth factor I (IGF\u2010I) in hepatocarcinogenesis, the clinical data about IGF\u2010I in patients with hepatocellular carcinoma (HCC) are scarce and controversial. To the authors' knowledge, this is the first prospective study investigating the longitudinal correlation between modifications in serum IGF\u2010I levels and the development of HCC in a cohort of patients with hepatitis C virus (HCV)\u2010related cirrhosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>One hundred fourteen consecutive patients with HCV\u2010related Child Grade A cirrhosis were followed prospectively at the Second University of Naples for 56.4 \u00b1 12.0 months with ultrasound examinations of the liver and serum \u03b1\u2010fetoprotein determination every 6 months. At each clinical evaluation, the severity of disease was graded according to the established Child\u2013Pugh scoring system. Serum IGF\u2010I levels were measured prospectively at the study entry and at least every 12 months throughout follow\u2010up.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Twenty patients (19.2%) developed HCC during follow\u2010up. Eleven of these patients had persistent Child Grade A cirrhosis for the whole study, whereas the other 9 patients developed HCC after their cirrhosis progressed from Child Grade A to Grade B. In patients who remained free of HCC for the whole study, serum IGF\u2010I concentrations did not modify significantly during follow\u2010up. Conversely, in patients who developed HCC, IGF\u2010I levels decreased significantly during follow\u2010up (from 72.6 \u00b1 29.9 \u03bcg\/L to 33.8 \u00b1 14.5 \u03bcg\/L; <jats:italic>P<\/jats:italic> = 0.001). In these patients, the significant decrease occurred both in patients with persistent Child Grade A cirrhosis and in patients with cirrhosis that progressed from Child Grade A to Grade B. The reduction in IGF\u2010I level preceded the diagnosis of HCC by 9.3 \u00b1 3.1 months.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>This prospective study demonstrates that, in patients with HCV\u2010related cirrhosis, 1) the development of HCC is accompanied by a significant reduction of serum IGF\u2010I levels independent of the grade of impairment of liver function; and 2) modification of the IGF\u2010I level precedes the morphologic appearance of HCC, permitting a precocious diagnosis of the tumor. Cancer 2002;95:2539\u201345. \u00a9 2002 American Cancer Society.<\/jats:p><jats:p>DOI 10.1002\/cncr.11002<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.11002","type":"journal-article","created":{"date-parts":[[2002,12,5]],"date-time":"2002-12-05T09:08:29Z","timestamp":1039079309000},"page":"2539-2545","source":"Crossref","is-referenced-by-count":81,"title":["Serum insulin\u2010like growth factor I evaluation as a useful tool for predicting the risk of developing hepatocellular carcinoma in patients with hepatitis C virus\u2010related cirrhosis"],"prefix":"10.1002","volume":"95","author":[{"given":"Gherardo","family":"Mazziotti","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Sorvillo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Filomena","family":"Morisco","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonella","family":"Carbone","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mario","family":"Rotondi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gianfranca","family":"Stornaiuolo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Davide F.","family":"Precone","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michele","family":"Cioffi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanni B.","family":"Gaeta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicola","family":"Caporaso","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlo","family":"Carella","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2002,12,3]]},"reference":[{"key":"e_1_2_5_2_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(20000701)89:1<53::AID-CNCR8>3.0.CO;2-6"},{"key":"e_1_2_5_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9343(99)00374-5"},{"key":"e_1_2_5_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(01)00130-1"},{"key":"e_1_2_5_5_2","first-page":"249","article-title":"The insulin\u2010like growth factor 1 receptor: a key to tumor growth?","volume":"55","author":"Baserga R","year":"1995","journal-title":"Cancer Res."},{"key":"e_1_2_5_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0304-419X(97)00007-3"},{"key":"e_1_2_5_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1659742"},{"key":"e_1_2_5_8_2","first-page":"2463","article-title":"The insulin\u2010like growth factor I receptor protects tumor cells from apoptosis in vitro","volume":"55","author":"Resnicoff M","year":"1995","journal-title":"Cancer Res."},{"key":"e_1_2_5_9_2","first-page":"3739","article-title":"Correlation between apoptosis, tumorigenesis, and levels of insulin\u2010like growth factor I receptors","volume":"55","author":"Resnicoff M","year":"1995","journal-title":"Cancer Res."},{"issue":"3","key":"e_1_2_5_10_2","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1159\/000053160","article-title":"Insulin\u2010like growth factor\u2010I and Binding Protein\u20103 and risk of cancer","volume":"51","author":"Giovannucci E","year":"1999","journal-title":"Hormone Res."},{"key":"e_1_2_5_11_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.279.5350.563"},{"key":"e_1_2_5_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(97)10384-1"},{"key":"e_1_2_5_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/91.7.620"},{"key":"e_1_2_5_14_2","doi-asserted-by":"publisher","DOI":"10.1136\/mp.54.3.138"},{"key":"e_1_2_5_15_2","first-page":"589","article-title":"Radioimmunoassay of serum IGF\u2010I and IGF\u2010II in patients with chronic liver diseases and hepatocellular carcinoma with or without hypoglycemia","volume":"112","author":"Wu JC","year":"1988","journal-title":"J Lab Clin Med."},{"key":"e_1_2_5_16_2","first-page":"1744","article-title":"Circulating growth hormone and insulin\u2010like growth factor\u2010I in non\u2010alcoholic liver cirrhosis with or without superimposed hepatocarcinoma: evidence of an altered circadian rhythm","volume":"88","author":"Buzzelli G","year":"1995","journal-title":"Am J Gastroenterol."},{"key":"e_1_2_5_17_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0215(20000701)87:1<118::AID-IJC17>3.0.CO;2-W"},{"key":"e_1_2_5_18_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.78.3.744"},{"key":"e_1_2_5_19_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.80.8.2534"},{"key":"e_1_2_5_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/bjs.1800600817"},{"key":"e_1_2_5_21_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.138.7.2645"},{"key":"e_1_2_5_22_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.18.12181"},{"key":"e_1_2_5_23_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840130406"},{"key":"e_1_2_5_24_2","first-page":"3831","article-title":"Increased expression of the insulin\u2010like growth factor I (IGF\u2010I) receptor gene in hepatocellular carcinoma cell lines: implications of IGF\u2010I receptor gene activation by hepatitis B virus X gene product","volume":"56","author":"Kim SO","year":"1996","journal-title":"Cancer Res."},{"key":"e_1_2_5_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510230602"},{"key":"e_1_2_5_26_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1746.1997.tb00412.x"},{"key":"e_1_2_5_27_2","first-page":"98","article-title":"Localization of insulin\u2010like growth factor II and hepatitis B virus mRNAs and proteins in human hepatocellular carcinomas","volume":"64","author":"Lamas E","year":"1991","journal-title":"Lab Invest."},{"key":"e_1_2_5_28_2","doi-asserted-by":"crossref","first-page":"3316","DOI":"10.1210\/jcem.83.9.5082","article-title":"Insulin\u2010like growth factor binding protein\u20103: a novel biomarker for the assessment of the synthetic capacity of hepatocytes in liver cirrhosis","volume":"83","author":"Shaarawy M","year":"1998","journal-title":"J Clin Endocrinol Metab."},{"key":"e_1_2_5_29_2","first-page":"439","volume-title":"Endocrinology","author":"Clemmons DR","year":"2001"},{"key":"e_1_2_5_30_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199104043241401"},{"key":"e_1_2_5_31_2","first-page":"760","article-title":"Transforming growth factor\u2010beta 1 (TGF\u2010\u03b21) and TGF\u2010\u03b21 receptor in normal, cirrhotic and neoplastic human liver","volume":"21","author":"Bedossa P","year":"1995","journal-title":"Hepatology."},{"key":"e_1_2_5_32_2","first-page":"785","article-title":"Expression of platelet\u2010derived growth factor and its receptor in human liver and during active hepatic fibrinogenesis","volume":"148","author":"Pinzani M","year":"1996","journal-title":"Am J Pathol."},{"key":"e_1_2_5_33_2","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.10170"},{"key":"e_1_2_5_34_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840060432"},{"key":"e_1_2_5_35_2","first-page":"309","volume-title":"Etiology, pathology, and treatment of hepatocellular carcinoma in North America","author":"Van Thiel DH","year":"1992"},{"key":"e_1_2_5_36_2","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1001\/jama.1975.03260010040018","article-title":"\u03b1\u2010Fetoprotein in nonneoplastic hepatic disorders","volume":"233","author":"Bloomer JR","year":"1975","journal-title":"JAMA."},{"key":"e_1_2_5_37_2","first-page":"856","article-title":"\u03b1\u2010Fetoprotein (AFP) in benign liver disease: evidence that normal liver regeneration does not induce AFP synthesis","volume":"74","author":"Alpert E","year":"1978","journal-title":"Gastroenterology."},{"key":"e_1_2_5_38_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199109053251002"},{"key":"e_1_2_5_39_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840190111"}],"container-title":["Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcncr.11002","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cncr.11002","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T09:38:35Z","timestamp":1760261915000},"score":1,"resource":{"primary":{"URL":"https:\/\/acsjournals.onlinelibrary.wiley.com\/doi\/10.1002\/cncr.11002"}},"subtitle":["A prospective study"],"short-title":[],"issued":{"date-parts":[[2002,12,3]]},"references-count":38,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2002,12,15]]}},"alternative-id":["10.1002\/cncr.11002"],"URL":"https:\/\/doi.org\/10.1002\/cncr.11002","archive":["Portico"],"relation":{},"ISSN":["0008-543X","1097-0142"],"issn-type":[{"value":"0008-543X","type":"print"},{"value":"1097-0142","type":"electronic"}],"subject":[],"published":{"date-parts":[[2002,12,3]]}}}